The REACTplusNMES Trial: A Double-blinded RCT

NCT ID: NCT06127602

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2026-05-31

Brief Summary

The aim of this study is to compare the effectiveness of 6-weeks of reactive balance training (REACT) with and without neuromuscular electrical stimulation (NMES) to paretic lower limb muscles on biomechanical, clinical, neuromuscular and neuroplastic outcomes of reactive balance control. This project is a Phase-I study and incorporates a double-blinded, randomized controlled trial design.

Methods: Forty-six individuals with chronic stroke will be recruited and screened for determining their eligibility for the study. Once enrolled, they will be randomized into either of the two groups: intervention group (23 participants) and control group (23 participants). Both groups will undergo series of pre-training assessments which includes a postural disturbance in the form of a slip- or trip-like perturbations and walking tests in laboratory environment. After the pre-training assessment, individuals will undergo 6-weeks of training (2 hour per session, 2 sessions per week). The intervention group will receive NMES with the REACT training and the control group will receive ShamNMES. NMES will be applied to the different muscle groups of the paretic lower limb using an advanced software which is able to synchronize muscle activation with the time of perturbation onset and according to the phases of gait. After training, both groups will again be tested on all the assessments performed pre training.

This study will help us understand the immediate therapeutic and mechanistic effects of REACT+NMES and inform stroke rehabilitation research and clinical practice. Our study will provide foundational evidence for future use of NMES to implement clinically applicable neuromodulation adjuvants to reactive balance training, which could be leveraged for designing more effective future interventions for fall-risk reduction.

Detailed Description

1.0 Background/Scientific Rationale Interventions such as conventional balance and exercise training constitute a major part of stroke rehabilitation and improve volitional balance control and gait in people with chronic hemiparetic stroke (PwCHS). However, they seldom target reactive balance (compensatory postural responses such as stepping) that forms the first line of defense while recovering from a balance loss. Reactive balance in PwCHS is affected by deficits in perturbation-evoked neuromuscular and biomechanical responses especially during gait. Further, previous research has shown that stability and adaptions to repeated perturbations is more affected on paretic compared to non-paretic limb. Thus, paretic limb deficits are postulated to be key contributors of falls in ambulatory PwCHS. Perturbation-based reactive balance training (REACT) is widely recognized as an intervention that reduces falls by improving fall-resisting skills. In the past five years, there is a 3-fold increase in perturbation training research in PwCHS (mostly low impairment). Thus, limited evidence exists for PwCHS with severe motor impairment who might not show similar tolerance or learning abilities.

Complementing REACT with interventions known to facilitate paretic limb performance and motor learning (i.e., neuromuscular electrical stimulation, NMES) can improve therapeutic effects of REACT and hence its clinical translation for PwCHS and other populations that could benefit from fall-risk reduction. While it is established that REACT programs and NMES can induce motor learning in behavioral variables, there is limited evidence on neuroplastic changes and exact neural mechanisms underlying these behavioral changes (especially during REACT). Similar to the precision medicine approach, modifiable causative factors, contributors, and mediators to falls must be targeted when designing effective falls prevention interventions that reduce training times and/or facilitate the inclusion of persons with high impairment.

This project aims to describe whether a specific pattern of lower limb muscle stimulation could modify the recovery response after an unexpected perturbation in the form of a slip and/or trip in individuals with stroke. Also, this study aims to examine the effectiveness of 6-weeks of reactive balance training (REACT) with and without neuromuscular electrical stimulation (NMES) to paretic lower limb muscles on biomechanical, clinical, neuromuscular and neuroplastic outcomes of reactive balance control.

2.0 Objectives/Aims

The specific aims of this study are below:

Aim 1: To examine effects of synchronous REACT+NMES on reactive balance control and clinical outcomes among people with chronic stroke with moderate to severe motor impairment.

H1.1: REACT+NMES will induce greater improvement in biomechanical outcomes of reactive balance (reactive stability, limb support) resulting in fewer laboratory falls post-training than REACT+ShamNMES (at 6 weeks).

H1.2: The improvements in reactive balance control in REACT+NMES will translate to greater improvement in clinical outcomes of balance (mini-BEST test), gait (10m walk test) and falls-efficacy (Activities specific Balance Confidence scores) than REACT. H1.3: The improvements in reactive balance control will also translate to reduced falls during overground gait-slips after REACT+NMES.

Aim 2: To examine neuromuscular and neuroplastic effects of REACT+NMES in PwCHS with moderate to severe motor impairment.

H2.1. REACT+NMES will induce greater neuromuscular (muscle synergy #s and activations) and neuroplastic (perturbation evoked potentials- PEPs) changes post-training than REACT (at 6 weeks).

H2.2: Baseline PEP amplitude and training-induced neuroplastic changes in PEP's will correlate with the training-induced improvements in biomechanical and neuromuscular responses.

3.0 Research Design This study trial employs a two-arm, double-blinded, randomized controlled trial (RCT) design This study will examine efficacy and feasibility of REACT-NMES intervention compared to REACT+ShamNMES among PwCHS with moderate to severe motor impairment (Aim 1 and 2) A sample size of 46 chronic stroke survivors will be enrolled, undergo initial screening and pre-training assessment, and then randomized into two groups (intervention and control). Next, both groups will undergo 6-weeks of in-lab reactive balance training (2x/week, total 12 sessions). After training, participants in both groups will undergo a post-training assessment, which will include all the tests performed in the pre-training assessment.

Study overview: All participants will undergo the following procedures.

• Session 1 (Week 1): Initial screening (2 hours)
• Session 2 (Week 2): Pre-test (total 4 hours)
• Session 3-15 (Week 3-8): Training sessions (2 hours/session, 2 times/week for 6 weeks) (total: 24 hours)
• Session 16 (Week 9): Post-test (total 4 hours)

Conditions

Stroke, Ischemic; Stroke Hemorrhagic; Stroke, Cerebrovascular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

REACT-NMES: Intervention condition

The REACT-NMES group will undergo 6 weeks of reactive balance training with NMES involving 12 one-hour sessions (twice a week). Each session will begin with NMES parameter setup where the current amplitude will be customized to individual "maximal tolerable" levels for a strong yet comfortable experience. NMES settings will include moderate to high intensity (30-50mA) and low frequency (20-45Hz) to target motor nerve thresholds. The REACT-NMES group will wear a footswitch on their paretic shoe for triggering the slips during walking and for NMES synchronization. NMES will be delivered to the paretic limb quadriceps muscles for 500 milliseconds after slip onset.

Group Type: EXPERIMENTAL

Reactive balance training with Neuromuscular Electrical Stimulation

Intervention Type: BEHAVIORAL

REACT-NMES group: The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have \< 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level. NMES will be delivered to the vastus lateralis synchronously with the perturbation, which will always occur 50 ms after slip-onset and last for 450 ms including the period between liftoff to touchdown of the first compensatory step.

REACT: Control condition

The REACT group will undergo 6 weeks involving 12 one-hour sessions (twice a week) of reactive balance training with ShamNMES. To prevent psychological bias and unblinding, sub-sensory stimulation will be used. ShamNMES will employ low intensity (0-10mA) and high frequency (50-100Hz), staying 20% below the sensory nerve threshold without inducing muscle contraction. The REACT group will wear a footswitch on their paretic shoe for triggering the slips during walking and for ShamNMES synchronization. ShamNMES (control) will be delivered after compensatory step touchdown to avoid interference with balance recovery.

Group Type: ACTIVE_COMPARATOR

Reactive balance training without Neuromuscular Electrical Stimulation

Intervention Type: BEHAVIORAL

REACT group: The REACT group will undergo the same reactive balance training (in terms of type, dosage: intensity, frequency) as the REACT-NMES group. The only difference will be that the REACT group will receive ShamNMES for same time after the compensatory step touchdown. The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have \< 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level.

Interventions

Reactive balance training with Neuromuscular Electrical Stimulation

REACT-NMES group: The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have \< 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level. NMES will be delivered to the vastus lateralis synchronously with the perturbation, which will always occur 50 ms after slip-onset and last for 450 ms including the period between liftoff to touchdown of the first compensatory step.

Intervention Type: BEHAVIORAL

Reactive balance training without Neuromuscular Electrical Stimulation

REACT group: The REACT group will undergo the same reactive balance training (in terms of type, dosage: intensity, frequency) as the REACT-NMES group. The only difference will be that the REACT group will receive ShamNMES for same time after the compensatory step touchdown. The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have \< 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Age group: 18-90 years.
• Presence of hemiparesis.
• Onset of stroke (> 6 months).
• Ability to walk at least for 2 minutes on the treadmill with or without ankle foot orthosis.
• Can understand and communicate in English.
• Cognitively and behaviorally capable of complying with the regimen (Mini-Mental State Examination > 25/30).
• No history or recent use (i.e., past 6 weeks) of any Neuromuscular electrical stimulation device to leg muscles during walking (e.g., Bioness, Walkaide).

Exclusion Criteria

• Subjects will not proceed with the test if any of the following occurs at baseline measurement: 1) HR > 85% of age-predicted maximal heart rate (HRmax) (HRmax = 220 - age), 2) systolic blood pressure (SBP) > 165 mmHg and/or diastolic blood pressure (DBP) > 110 mmHg during rest, or 3) oxygen saturation (measured by pulse oximeter) < 95% during rest.
• Body weight of more than 250 lbs.
• Spasticity (Ashworth scale > 2).
• Loss of protective sensations on the paretic leg (indicated by inability to perceive the 5.07/10 g on Semmes-Weinstein Monofilament) or inability to feel the NMES.
• Severe osteoporosis (indicated by T score < -2)
• Cognitive impairment (indicated by Mini-Mental State Exam score<25)
• Global Aphasia (indicated by <71% on the Mississippi Aphasia Screening Test).
• Subjects with Chedoke McMaster Leg Assessment Scale score (> 4).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Tanvi Bhatt

Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tanvi Bhatt

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rudri Purohit, MS

Role: CONTACT

rpuroh2@uic.edu

312-413-9772

Swaranka Deshmukh, MS

Role: CONTACT

sdeshm9@uic.edu

312-355-3988

Facility Contacts

Tanvi Bhatt, PhD

Role: primary

tbhatt6@uic.edu

312-355-4443

Rudri Purohit, MS

Role: backup

rpuroh2@uic.edu

312-413-9772

References

Kesar T, Chou LW, Binder-Macleod SA. Effects of stimulation frequency versus pulse duration modulation on muscle fatigue. J Electromyogr Kinesiol. 2008 Aug;18(4):662-71. doi: 10.1016/j.jelekin.2007.01.001. Epub 2007 Feb 21.

Reference Type: BACKGROUND

PMID: 17317219 (View on PubMed)

Varas-Diaz G, Bhatt T. Application of neuromuscular electrical stimulation on the support limb during reactive balance control in persons with stroke: a pilot study. Exp Brain Res. 2021 Dec;239(12):3635-3647. doi: 10.1007/s00221-021-06209-2. Epub 2021 Oct 5.

Reference Type: RESULT

PMID: 34609544 (View on PubMed)

Pereira S, Mehta S, McIntyre A, Lobo L, Teasell RW. Functional electrical stimulation for improving gait in persons with chronic stroke. Top Stroke Rehabil. 2012 Nov-Dec;19(6):491-8. doi: 10.1310/tsr1906-491.

Reference Type: RESULT

PMID: 23192714 (View on PubMed)

Dusane S, Bhatt T. Effect of Multisession Progressive Gait-Slip Training on Fall-Resisting Skills of People with Chronic Stroke: Examining Motor Adaptation in Reactive Stability. Brain Sci. 2021 Jul 7;11(7):894. doi: 10.3390/brainsci11070894.

Reference Type: RESULT

PMID: 34356128 (View on PubMed)

Kottink AI, Oostendorp LJ, Buurke JH, Nene AV, Hermens HJ, IJzerman MJ. The orthotic effect of functional electrical stimulation on the improvement of walking in stroke patients with a dropped foot: a systematic review. Artif Organs. 2004 Jun;28(6):577-86. doi: 10.1111/j.1525-1594.2004.07310.x.

Reference Type: RESULT

PMID: 15153151 (View on PubMed)

Other Identifiers

2023-1233

Identifier Type: -

Identifier Source: org_study_id